Search

ABCC8 and KCJN11 mutations cause the most severe diazoxide-resistant forms of congenital hyperinsulinism (CHI). Somatostatin analogues are considered as secondline treatment in diazoxide-unresponsive cases. Current treatment protocols include the first-generation somatostatin analogue octreotide, although pasireotide, a second-generation somatostatin analogue, might be more effective in reducing insulin secretion. Herein we report the first off-label use of pasireotide in a boy with a severe therapy-resistant form of CHI due to a homozygous ABCC8 mutation. After partial pancreatectomy, hyperinsulinism persisted; in an attempt to prevent further surgery, off-label treatment with pasireotide was initiated. Short-acting pasireotide treatment caused high blood glucose level shortly after injection. Long-acting pasireotide treatment resulted in more stable glycemic control. No side effects (e.g., central adrenal insufficiency) were noticed during a 2-month treatment period. Because of recurrent hypoglycemia despite a rather high carbohydrate intake, the boy underwent near-total pancreatectomy at the age of 11 months. In conclusion, pasireotide treatment slightly improved glycemic control without side effects in a boy with severe CHI. However, the effect of pasireotide was not sufficient to prevent near-total pancreatectomy in this case of severe CHI.

Somatostatin analogues, suchas octreotide and lanreotide, are commonly used in the management of enterocutaneous fistula. We report a case of severe and prolonged hyperglycemia that occurred in a patient after receiving a one-time dose of lanreotide, who had previously been stable on octreotide and did not have a history of diabetes mellitus. Management of the patient's hyperglycemia while receiving parenteral nutrition is described.

Although neuroendocrine tumours (NETs) are intensively studied, their diagnosis and consequently personalised therapy management is still puzzling due to their tumoral heterogeneity. In their theragnosis algorithm, receptor somatostatin scintigraphy takes the central place, the diagnosis receptor somatostatin analogue (RSA) choice depending on laboratory experience and accessibility. However, in all cases, the results depend decisively on correct radiotracer tumoral uptake quantification, where unfortunately there are still unrevealed clues and lack of standardization. We propose an improved method to quantify the biodistribution of gamma-emitting RSA, using tissular corrected uptake indices. We conducted a bi-centric retrospective study on 101 patients with different types of NETs. Three uptake indices obtained after applying new corrections to areas of interest drawn for the tumour and for three reference organs (liver, spleen and lung) were statistically analysed. For the corrected pathological uptake indices, the results showed a significant decrease in the error of estimating the occurrence of errors and an increase in the diagnostic predictive power for NETs, especially in the case of lung-referring corrected index. In conclusion, these results support the importance of corrected uptake indices use in the analysis of 99mTcRSA biodistribution for a better personalised diagnostic accuracy of NETs patients.

VIPoma is an unusual neuroendocrine neoplasm that autonomously secretes VIP. It is associated with secretory diarrhea and electrolyte disturbances. Herein we report a case of a male patient, who was hospitalized in the Department of Endocrinology in Hedi Chaker Hospital, Sfax, Tunisia. He presented VIPoma syndrome, with hepatic metastases at diagnosis. He had a history of chronic, watery diarrhea. He was dehydrated with many electrolytic disorders as hypokalemia, hyponatremia and metabolic acidosis. Abdominal CT scan showed a heterogeneous mass in the pancreatic head with multiple hepatic lesions. A high VIP hormone level was found. Histological study of a liver biopsy revealed hepatic metastases of neuroendocrine carcinoma. The patient received analogues of somatostatin and systemic chemotherapy, with a transient symptomatic relief. Sadly the patient was lost to follow-up.

BACKGROUND: In the last decades, the incidence of neuroendocrine neoplasia (NEN) increased from 1 to 5 new diagnoses/100,000 persons/year. The synthetic somatostatin analogues (SSAs) represent the first-choice treatment for both functionally active and inactive gastro-enteric-pancreatic NEN. This systematic review examines the role of octreotide long-acting release (LAR) in combination with other therapies for NEN management. METHODS: Primary outcomes were the disease control rate and the progression free survival (PFS), defined as the time between treatment initiation and progression of disease. Secondary outcomes were overall survival (OS) and safety. RESULTS: This systematic review identified 13 studies, concerning the use of octreotide LAR in association with other therapies in advanced NENs and included 1,206 patients. Patients were treated with octreotide LAR in combination with other drugs, mainly with everolimus (404 patients, 35%), but even with Peptide Receptor Radionuclide Therapy, bevacizumab, interferon or fluoride-derivatives. Disease control was observed in 85% cases with SSAs in combination with other therapies; PFS ranged from 15 to 16.4 months and OS from 25 to 61.9 months. SSAs are very well tolerated drugs, with few side effects which are usually mild, not requiring drug withdrawn. CONCLUSIONS: The review summarizes the effectiveness and available safety data on octreotide LAR in combination with other therapies in patients with NEN and may provide suggestions to address the therapeutic strategy. Further comparative head-to-head studies are needed to understand which is the best combination treatment for patients with progressive NEN after failure of first-line therapy.

Background Gastroenteropancreatic neuroendocrine tumors (GEP‐NETs) are increasingly common malignancies and tend to have favorable long‐term prognoses. Somatostatin analogues (SSA) are a first‐line treatment for many NETs. Short‐term experiments suggest an association between SSAs and hyperglycemia. However, it is unknown whether there is a relationship between SSAs and clinically significant hyperglycemia causing development of diabetes mellitus (DM), a chronic condition with significant morbidity and mortality. Aim In this study, we aimed to compare risk of developing DM in patients treated with SSA vs no SSA treatment. Methods and Results Using the Surveillance, Epidemiology, and End Results (SEER) database and linked Medicare claims (1991‐2016), we identified patients age 65+ with no prior DM diagnosis and a GEP‐NET in the stomach, small intestine, appendix, colon, rectum, or pancreas. We used χ 2 tests to compare SSA‐treated and SSA‐untreated patients and multivariable Cox regression to assess risk factors for developing DM. Among 8464 GEP‐NET patients, 5235 patients had no prior DM and were included for analysis. Of these, 784 (15%) patients received SSAs. In multivariable analysis, the hazard ratio of developing DM with SSA treatment was 1.19, which was not statistically significant (95% CI 0.95‐1.49). Significant risk factors for DM included black race, Hispanic ethnicity, prior pancreatic surgery, prior chemotherapy, tumor size >2 cm, pancreas tumors, and higher Charlson scores. Conclusion DM was very common in GEP‐NET patients, affecting 53% of our cohort. Despite prior studies suggesting an association between SSAs and hyperglycemia, our analysis found similar risk of DM in SSA‐treated and SSA‐untreated GEP‐NET patients. Further studies are needed to better understand this relationship. As NET patients have increasingly prolonged survival, it is crucial to identify chronic conditions such as DM that these patients may be at elevated risk for.

INTRODUCTION: In the past the inability to control the hormone-excess-state was the main determinant of survival in patients with Functional Neuroendocrine Neoplasm syndromes (F-NENs). This could prove especially difficult because the pharmacological armamentarium available until relatively recently was limited. In the last few years there have been a marked increase in the therapeutic strategies available which have opened new pharmacotherapeutic approaches, but have also generated some controversies, uncertainties and confusion. AREAS COVERED: In this perspective, the authors briefly review the different F-NENs that are established as well as those proposed; the rationale for approaching their treatment and why both an approach to controlling their hormone-excess-state and their malignant nature is required in most cases; the current recommended initial pharmacotheraputic approach to controlling the hormone-excess-state of the different F-NENs; the secondary approaches to controlling the hormone-excess-state if the initial approach fails or resistance develops; and the approach to deal with the malignant nature of the NEN per se. Also discussed are the controversies the new treatments have generated particularly related to the timing of the diagnosis of the F-NEN, as well as the sequences of secondary treatments, and the exact role of PRRT. EXPERT OPINION: Unfortunately, except for patients with insulinomas(>90-95%), gastrinomas(

Background and Aims Recently, we performed a large randomized-controlled trial to assess the effects of the somatostatin analogue lanreotide on kidney function and kidney and liver volume in autosomal dominant polycystic kidney disease (ADPKD), the DIPAK-1 trial. Lanreotide had no effect on rate of kidney function decline, but slowed kidney and especially liver growth and is used for this indication in clinical practice1,2. A higher incidence of gallstones has been suggested with lanreotide use, but the exact size and implications of this problem are unknown. Therefore, we systematically studied the incidence of gallstones with lanreotide in ADPKD patients. Method In the DIPAK-1 trial, 305 ADPKD patients (age 18-60 years and eGFR 30-60 ml/1.73m2/min) were randomized to lanreotide or standard of care. MRIs were performed at baseline and end of study (120 weeks). For this post-hoc study, patients with a medical history of cholecystectomy (n=7) or absence of a MRI at the end of study (n=28) were excluded. For the remaining study population (n=270), all MRIs were assessed for presence of gallstones by two trained investigators blinded for study treatment and study period and in case of disagreeing results, an abdominal radiologist was consulted for a final assessment. For patients with gallstones additional follow up after the end of the trial was obtained. Results In 2 baseline and 8 end-of -study MRIs, it was not possible to identify the gallbladder, due to multiple adjacent liver cysts. Of the remaining 260 patients (age 48.5 years, female 49.6%, eGFR 50.0 ml/min/1.73m2), 14 patients (5,4%) had gallstones at baseline, of whom 5 were randomized to lanreotide and 9 to standard care. At the end of study, 32 patients (12,3%) had gallstones, of whom 21 patients had received lanreotide and 11 standard care. During the 120 week lasting study, new gallstones occurred in 17 out of 128 patients receiving lanreotide (13.3%) and 3 out of 132 patients receiving standard care (2.3%), rendering an adjusted Odds Ratio for gallstone formation with lanreotide use of 6.9 (95% Confidence Interval 1.9-24.7) p Of the 32 patients with gallstones at the end of study, seven experienced gallstone-associated complications. Three experienced a biliary pancreatitis (1 during and 2 after the study). Another one had signs of a chronic pancreatitis as accidental finding on imaging during the study, without having had symptoms. Furthermore, another 3 patients underwent a cholecystectomy for symptomatic gallstones after the study. Importantly, all patients with gallstone-associated complications were part of the subgroup of patients that developed de novo gallstones during lanreotide use in the study. Conclusion Lanreotide increases the risk of gallstone formation in ADPKD sevenfold. Gallstones were associated with severe complications, most occurring after the end of the trial. The benefit of somatostatin analogues to reduce kidney and liver size in ADPKD should therefore be weighed against the higher incidence of these adverse events, and patients and doctors should be aware of the risk of (symptomatic) gallstones with use of these drugs.

Background: Diagnosis of thyrotropin (TSH)-secreting pituitary adenomas (TSHoma) before surgery remains a challenge, especially for microadenomas. We aimed to establish a short-term somatostatin an...

Background Patients with metastatic small-intestinal neuroendocrine tumours (NET) have been shown to have a reduced quality of life compared to the general population and many have disabling symptoms during somatostatin analogue (SSA) treatment. The aim of this prospective study was to document the patient-reported symptoms, coping and quality of life during SSA treatment and to measure patients’ fat-soluble vitamin levels. Methods Patients with metastatic small-intestinal NET on treatment with long-acting SSA were included. Data on patient characteristics, blood samples, questionnaires (EORTC-QLQ-C30 and GI.NET-21) and structured patient interviews were collected at inclusion and after 1 year. Results Eighty-eight patients were included, 77 (88%) attended 1 year follow-up. Approximately 50% of patients reported symptoms, the most common symptoms at baseline and after 1 year follow-up were diarrhoea, flatulence, fatigue, abdominal discomfort and sore injection lumps. Diarrhoea and fatigue were reported as their main complaint, 23% had > 5 daily episodes of diarrhoea and 59% reported fatigue. However, patients reported a high perceived quality of life, high daily activity, coped with their symptoms and managed their daily life well. Deficiency of vitamin D (27%) and A (13%) were observed. Conclusions Patients with metastatic small-intestinal NET on SSA treatment reported a high frequency of symptoms. Minor improvements were seen after 1-year of follow-up, illustrating that many symptoms might be difficult to improve, or may not be recognised by the health service. Patients, however, generally reported a high quality of life. Care for NET patients on SSA treatment should include a regular systematic symptom registration and vitamin measurements.

Lanreotide autogel is a long-acting somatostatin analogue with proven efficacy and safety in patients with well-differentiated (WD) gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) in a prior randomized phase III trial (CLARINET). However, the CLARINET study only enrolled patients with Ki-67 index10%, and few patients of Asian ethnicity were included. We retrospectively analyzed the efficacy and safety of lanreotide in Korean patients with GEP-NETs in the daily practice setting. Between January 2015 and May 2018, 64 patients with metastatic WD GEP-NETs received lanreotide at Asan Medical Center, Seoul, Korea. Of them, 45 (70.3%) patients who received lanreotide as monotherapy were included in the current analysis. The most common primary tumor site was the pancreas (n = 22, 48.9%), followed by the rectum (10, 22.2%) and the small bowel (7, 15.6%). According to RECIST v1.1, a partial response was achieved in one patient (2.2%) and stable disease was achieved in 40 patients (88.9%). The median progression-free survival (PFS) was 16.4 months (95% confidence interval, 9.5-23.3 months). There were no differences in PFS according to the primary tumor site (p = 0.77). Hepatic tumor volume 25% and prior systemic therapy were significantly associated with poorer PFS in the multivariate analysis. Lanreotide is well-tolerated and effective for Korean patients with GEP-NETs in the daily practice setting.

Background: A long-acting somatostatin analogue (lanreotide) is used in the management of a diazoxide-unresponsive diffuse form of congenital hyperinsulinism (CHI). However, no reports of its use in patients with the focal form of CHI exist. Case 1: A 1-month-old boy diagnosed with diazoxide-unresponsive CHI due to a paternal heterozygous ABCC8 gene mutation showed partial response to octreotide. 18F-DOPA-PET/CT scan revealed a focal lesion in the pancreatic head. Surgical removal of the lesion was unsuccessful. He was switched to monthly lanreotide treatment at the age of 11 months, which stabilised his blood glucose over a 12-month period. Case 2: A 1-month-old boy with diazoxide-unresponsive CHI due to a paternal heterozygous KCNJ11 gene mutation was partially responsive to octreotide. 18F-DOPA-PET/CT scan confirmed a focal pancreatic head lesion. Over 6 months, he underwent 3 lesionectomies and afterwards responded to octreotide. At the age of 9 months, treatment was switched to monthly lanreotide. Currently, he is aged 3, with stable glycaemia, and improved fasting tolerance. Case 3: A 3-week-old girl with a paternal heterozygous ABCC8 gene mutation was unresponsive to diazoxide. 18F-DOPA-PET/CT scan confirmed a focal pancreatic head lesion. She responded to octreotide, and her parents preferred to avoid pancreatic surgery. At the age of 20 months, treatment was switched to monthly lanreotide, resulting in euglycaemia over the last 7 months. Conclusion: CHI patients with focal pancreatic head lesions are challenging, especially if not surgically amenable. Conservative treatment is preferable, and lanreotide might be an option. The therapeutic impact of lanreotide treatment in patients with the focal forms of CHI should be confirmed in prospective studies with close monitoring of the side effects.

Angioectasias (AD) belong to benign vascular malformations of the gastrointestinal tract and are responsible for about 4-7% of upper non variceal bleeding, 30-40% of small bowel occult bleeding and 3-40% of colonic bleeding episodes. Gastrointestinal haemorrhage secondary to AD represents an important diagnostic and therapeutic problem that negatively impacts on the quality of life of patients and heath care costs. Endoscopic interventions are the mainstay in both diagnosis and treatment of vascular malformations. However, in a substantial percentage of the cases, age of the patients, comorbidities, clinical severity of anaemia and blood loss as well as size, site and number of lesions prevent this therapeutic approach. Hormonal therapy, thalidomide and somatostatin analogues have been investigated for their potential role as rescue therapies in controlling AD bleeding although, thus far, no recommendations have been provided on their use in this clinical setting. In order to implement appropriate prescription of pharmacological agents to manage gastrointestinal bleeding due to ADs, the Italian Society of Gastroenterology (SIGE) nominated a panel of experts who reviewed the available clinical literature and produced practical clinical recommendations.

Background Primary hepatic neuroendocrine carcinoma (PHNEC) is extremely rare. The diagnosis of PHNEC remains challenging—partly due to its rarity, and partly due to its lack of unique clinical features. Available treatment options for PHNEC include surgical resection of the liver tumor(s), radiotherapy, liver transplant, transcatheter arterial chemoembolization (TACE), and administration of somatostatin analogues. Case presentation We report two male PHNEC cases and discuss the diagnosis and treatment options. Both cases presented with abdominal pain; case two also presented with symptoms of jaundice. The initial diagnosis for both cases was poorly differentiated grade 3 small-cell neuroendocrine carcinoma, based on imaging characteristics and the pathology of liver biopsies. Final diagnoses of PHNEC were arrived at by ruling out non-hepatic origins. Case one presented with a large tumor in the right liver lobe, and the patient was treated with TACE. Case two presented with tumors in both liver lobes, invasions into the left branch of hepatic portal vein, and metastasis in the hepatic hilar lymph node. This patient was ineligible for TACE and was allergic to the somatostatin analogue octreotide. This limited treatment options to supportive therapies such as albumin supplementation for liver protection. Patient one and two died at 61 and 109 days, respectively, following initial hospital admission. Conclusions We diagnosed both cases with poorly differentiated grade 3 small-cell PHNEC through imaging characteristics, immunohistochemical staining of liver biopsies, and examinations to eliminate non-hepatic origins. Neither TACE nor liver protection appeared to significantly extend survival time of the two patients, suggesting these treatments may be inadequate to improve survival of patients with poorly differentiated grade 3 small-cell PHNEC. The prognosis of poorly differentiated grade 3 small-cell PHNEC is poor due to limited and ineffective treatment options.

Context Discordant GH and IGF-I values are frequent in acromegaly. The clinical significance and its dependence on treatment modality and of glucose-suppressed GH (GHnadir) measurements remain uncertain. Objective To evaluate the effects of targeting either IGF-I or GH during somatostatin analogue (SA) treatment. Patients and Methods 84 patients with controlled acromegaly after surgery (n = 23) or SA (n = 61) underwent a GH profile including an OGTT, at baseline and after 12 months. SA patients were randomized to monitoring according to either IGF-I (n = 33) or GHnadir (n = 28). SA dose escalation was allowed at baseline and 6 months. Main outcome measures GHnadir and IGF-I at baseline and 12 months, and disease-specific Quality of Life (QoL). Results IGF-I and fasting GH levels were comparable between the surgery and the SA group, whereas GHnadir (µg/L) was lower in the surgery group (GHnadir 0.7 ± 0.1 vs 0.3 ± 0.1, P P = 0.02), which increased the number of concordantly controlled patients (P = 0.01). QoL was only mildly affected at baseline in all groups and did not changed consistently during the study. Conclusion (1) Discordant values in terms of high GH levels are prevalent in SA patients and more so if applying glucose-suppressed GHnadir; (2) targeting discordant levels of either GH or IGF-I translates into SA dose increase and improved biochemical control; (3) even though QoL was not improved in this study, we suggest biochemical assessment of disease activity to include glucose-suppressed GHnadir also in SA patients.

Dear Editor,We read with interest the expert opinion from Panzuto and colleagues [1] on the development of pancreatic exocrine insufficiency (PEI) secondary to somatostatin analogue (SSA) therapy i...

Acromegaly is caused by excessive growth hormone secretion, usually from pituitary adenomas. Somoatostatin analogues are widely used as primary or adjunctive therapy in the management of acromegaly. In this report, we present a case with remarkable shrinkage of a tumor after relatively short-term octreotide long-acting release (LAR) administration. During the 30-month follow-up after starting octreotide LAR, there was no recurrence of acromegaly with remarkable shrinkage of the tumor on pituitary magnetic resonance imaging. A literature review of the predictors for tumor shrinkage after the administration of somatostatin analogues in patients with acromegaly is also discussed in relation to this case.

AIM To describe real-world treatment patterns of gastrointestinal neuroendocrine tumors (GI NET). METHODS In this retrospective cohort study, we used 2009-2014 data from 2 United States commercial claims databases to examine newly pharmacologically treated patients using tabular and graphical techniques. Treatments included somatostatin analogues (SSA), cytotoxic chemotherapy (CC), targeted therapy (TT), interferon (IF) and combinations. We identified patients at least 18 years of age, with ≥ 1 inpatient or ≥ 2 outpatient claims for GI NET who initiated pharmacologic treatment from 7/1/09-6/30/14. A 6 mo clean period prior to first treatment ensured patients were newly treated. Patients were followed until end of enrollment or the study end date, whichever was first. RESULTS We identified 2258 newly treated GI NET patients: mean (SD) age was 55.6 years (SD = 9.7), 47.2% of the patients were between 55 and 64 years, and 48.8% were female. All regions of the United States were represented. 59.6% started first-line therapy with SSA monotherapy (964 with octreotide LAR, 380 with octreotide SA, and 1 with lanreotide), 33.3% CC, 3.6% TT, and 0.5% IF. The remainder received combinations. Mean follow up was 576 d. Overall mean first-line therapy duration was 361 d (449 d for SSA, 215 for CC, 267 for TT). 58.9% of patients had no pharmacological treatment beyond first line. The most common second-line was combination therapy with SSA. In graphical pattern analysis, there was no clear pattern visible after first line therapy. CONCLUSION In this study, 60% of patients initiated treatment with SSA alone or in combination. The relatively long time to discontinuation suggests possible sustained effectiveness and tolerability.

Neuroendocrine neoplasms (NEN) represent a heterogeneous group of malignancies generally characterized by low proliferation and indolent course. However, about half of the newly diagnosed cases are metastatic and require long-term systemic therapies. Areas covered: This review revises the literature to summarize the current knowledge upon safety of all systemic treatment options available. Thirty three different clinical studies have been considered, including 4 on somatostatin analogues (SSA), 5 on targeted therapies, 10 on peptide receptor radionuclide therapy (PRRT), and 14 on chemotherapy. Expert opinion: SSA are safe and well tolerated without any relevant severe adverse event and very low treatment discontinuation rate. Targeted therapies show a satisfying safety profile. Most adverse events are grade 1-2 and easy manageable with dose reduction or temporary interruption. PRRT is manageable and safe with a low rate of grade 3-4 adverse events. However, severe renal and hematologic toxicity may occur. Chemotherapy is usually considered after previous therapeutic lines. Therefore, these subjects are more susceptible to experience adverse events due to cumulative toxicities or poor performance status. The available systemic treatment options are generally well tolerated and suitable for long-term administration. Cumulative toxicity should be taken in account for the definition of therapeutic sequence.

Supplemental Digital Content is available in the text., IgA Nephropathy (IgAN) is a common cause of end-stage kidney disease worldwide. Unfortunately, the exact pathogenesis of IgAN remains uncertain without any targeted therapy. While kidney transplantation remains the gold standard treatment for those with end-stage kidney disease from IgAN, recurrence occurs frequently and may lead to early kidney transplant loss. Research has suggested that insulin-like growth factor-1 may play a role in mesangial cell proliferation in IgAN and Somatostatin may inhibit insulin-like growth factor-1. In this single case study, we report the use of octreotide, a somatostatin analogue, as a potential novel therapy for early recurrent IgAN post kidney transplant.

Background: Acromegaly is almost always caused by a pituitary adenoma and is associated with high morbidity and mortality when uncontrolled. Trans-sphenoidal removal of the adenoma is the mainstay of therapy, but fails to control the disease in a significant number of patients who require further treatment. Somatostatin analogues (SSAs) as monotherapy or in combination with growth hormone (GH)-receptor antagonists and/or dopamine agonists are used either alone or in combination following surgical failure to achieve disease control. The use of specific biomarkers may help to individualize the therapeutic plan after surgical failure and direct towards a more personalized approach. Methods: We report a 41-year-old man with acromegaly and residual disease after repeated surgery that was resistant to first-generation SSAs. Results: Biochemical and tumor control were achieved following the administration of a second-generation SSA, pasireotide, combined with pegvisomant, both at maximal doses and along with cabergoline. Histology specimens showed a sparsely-granulated GH-immunostaining pituitary adenoma with intense positivity for somatostatin receptors 2 and 5 and low levels of E-cadherin. Conclusion: Personalized medical therapy guided by currently available biomarkers, such as immunohistochemically-characterized receptor profiling or adhesion molecules, resulted in controlled insulin-like growth factor-1 (IGF-1) and GH levels and symptom alleviation following the combination of three drug-classes.

Purpose The antiproliferative properties of lanreotide autogel (LAN) in gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) were demonstrated in the CLARINET study. However, there is limited literature regarding factors that affect progression-free survival (PFS) in patients with GEP NENs treated with LAN. Methods We identified a total of 191 treatment-naive patients with advanced GEP NENs and positive SSTR uptake on imaging (Octreoscan or 68Gallium DOTATATE Positron Emission Tomography [68GaPET]) who received first-line LAN monotherapy, albeit at various starting doses (60, 90 or 120 mg/month). A group of 102 patients who initiated treatment at the standard dose of 120 mg/month were included in the study and further evaluated by univariate and multivariate analyses to identify predictors of PFS. Results The location of tumour primary was in the small bowel in 63 (62%), pancreas in 31 (30%) and colon/rectum in 8 patients (8%). The tumours were well-differentiated, and the majority were grade 1 (52%), or 2 (38%). About 60% of cases had progressive disease at the time of treatment initiation. Most patients with available pretreatment nuclear medicine imaging (Octreoscan or 68Ga PET) had a Krenning score of 3 (44%) or 4 (50%). The median PFS for the entire cohort was 19 months (95% CI 12, 26 months). The univariate analysis demonstrated that grade 2 tumours, progressive disease at baseline and metastatic liver disease were associated with a significantly shorter PFS, while other evaluated variables did not affect PFS at a statistically significant level. However, at multivariate analysis only the tumour grade remained statistically significant. Conclusions The current study showed that, of many evaluated variables, only the tumour grade was predictive of PFS duration and this should be considered during patient selection for treatment.

Purpose: Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy.

Background and aim: In autosomal dominant polycystic kidney disease (ADPKD) cardiac abnormalities have been observed before the onset of hypertension or renal dysfunction. We sought to characterize, in ADPKD patients, left ventricular (LV) function and its changes after somatostatin-analogue octreotide-LAR treatment. Methods: In a 1:1:1 cross-sectional study, we evaluated LV function by speckle-tracking echocardiography in 34 ADPKD patients from one ALADIN-trial center and in 34 age- and gender-matched healthy controls and 34 equally-matched renal controls with non-cystic chronic kidney disease. Changes in LV function were compared in the 16 and 18 ADPKD patients originally randomized to 3 year-treatment with octreotide-LAR or placebo, respectively. Results: LV twist and untwisting rates were lower in ADPKD patients that in healthy or renal controls (6.1 ± 2.6° vs. 11.1 ± 2.1° and 10.2 ± 3.7°; -49.5 ± 18.1°/s vs. -79.8 ± 12.2°/s and -84.3 ± 25.9°/s, respectively, all p < 0.001). The correlation between LV mass or diastolic BP and untwisting rate was positive in ADPKD patients (r = 0.38, p = 0.025 and r = 0.44, p = 0.011, respectively), not significant in healthy controls and negative in renal controls (r = -0.38; p = 0.023 and r = -0.40, p = 0.012, respectively. LV untwisting rate improved from -49.9 ± 18.6°/s to -70.3 ± 27.5°/s with octreotide-LAR, but did not change with placebo (p = 0.027 for treatment effect). At adjusted linear regression analysis, octreotide-LAR therapy emerged as the only independent predictor of untwisting rate improvement at final visit [beta coefficient -0.504 (95% CI -46.905--6.367), p = 0.014]. Conclusions: In ADPKD patients LV function is early impaired. Somatostatin-analogue therapy might help in preventing or ameliorating LV dysfunction in this population. Clinical Trial Registration http://www.clinicaltrials.gov, NCT0030928.

Acromegaly is a rare disease resulting from hypersecretion of growth hormone (GH) and insulin‐like growth factor 1 (IGF1) typically caused by pituitary adenomas, which is associated with increased mortality and morbidity. Somatostatin analogues (SSAs) represent the primary medical therapy for acromegaly and are currently used as first‐line treatment or as second‐line therapy after unsuccessful pituitary surgery. However, a considerable proportion of patients do not adequately respond to SSAs treatment, and therefore, there is an urgent need to identify biomarkers predictors of response to SSAs. The aim of this study was to examine E‐cadherin expression by immunohistochemistry in fifty‐five GH‐producing pituitary tumours and determine the potential association with response to SSAs as well as other clinical and histopathological features. Acromegaly patients with tumours expressing low E‐cadherin levels exhibit a worse response to SSAs. E‐cadherin levels are associated with GH‐producing tumour histological subtypes. Our results indicate that the immunohistochemical detection of E‐cadherin might be useful in categorizing acromegaly patients based on the response to SSAs., This work was supported by grants from the ISCIII‐Subdirección General de Evaluación y Fomento de la Investigación co‐funded with Fondos FEDER (PI13/02043 to A.S‐M. and PI16/00175 to A.S‐M. and D.A.C), Junta de Andalucía (A‐0023‐2015, A‐0003‐2016 to A.S‐M, CTS‐1406, BIO‐0139 to J.P.C. and R.M.L.) and CIBERobn. CIBER is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain. D.A.C. was supported by a research contract from the “Nicolás Monardes” program of the Andalusian Ministry of Health (C‐0015‐2014). Part of the analyses included in this study was carried out within the REMAH (“Spanish molecular registry of pituitary adenomas”) project, supported by Novartis Oncology as well as by the Andalusian and Spanish Societies of Endocrinology and Nutrition (SAEDYN and SEEN, respectively).

Introduction/Background: Thyrotropin secreting pituitary adenomas (TSH-oma) are a rare cause of hyperthyroidism. They account for Clinical Case: A 61 years old gentleman with a history of hypothyroidism diagnosed three years before presentation to the Pituitary clinic. He was treated with Levothyroxine. On clinical examination, he had mild tremor and warm sweaty palms with no stigmata of Grave’s disease. The thyroid function test showed elevated free T4 of 3.6 ng/dl (0.9-1.7), elevated free T3 of 8.6 pg/ml (2.0-4.4), and a high TSH level of 9.10 μIU/ml (0.27-4.20). His prolactin level was mildly elevated at 24.8 ng/ml(4.0-15.2). Testosterone, IGF-1, and cortisol levels were normal. An MRI of his pituitary gland showed large pituitary macroadenoma with supra-sellar extension and mild compression of the optic nerve. He had an elevated alpha subunit of 5.6 ng/ml ( Conclusion: Somatostatin analogues can be used as a primary treatment for thyrotropin secreting pituitary adenomas when the patient is unable or unwilling to undergo surgery. It is use is associated with normalization of thyroid function and in some cases with a reduction in the adenoma size.

Therapies for acromegaly aim at normalizing hormonal excess and controlling tumor growth . Therapeutic approaches are surgery, pharmacotherapy and radiotherapy. Area covered: This review focuses on the role of medical therapy of acromegaly, comparing the efficacy of somatostatin analogues (SSA), dopamine-agonists (DA) and pegvisomant (PEG), the three available drug classes for treating acromegaly. To clarify the difference in response rates reported in the literature for these therapies, we performed a search for original articles published in PubMed. SSA represent the first-line approach to medical treatment. This therapy is effective in controlling acromegaly in about 40% of patients, however there are great differences in the reported hormonal efficacy of SSA in the different series. In patients partially resistant to SSA, cabergoline can be added when hormonal levels are close to normalization, resulting effective in control IGF-I levels in 43% of patients. In patients with higher hormonal levels PEG is indicated, normalizing IGF-I levels in 79.8% and 80.6% of cases when used in monotherapy or in combination with SSA. Pasireotide, the newly developed SSA multi-ligand receptor, represents a new option in SSA resistant patients. Expert commentary: Medical therapy represents an important therapeutic option resulting safe and effective in controlling acromegaly in a high percentage of patients. The best treatment should be individually tailored for each patient, taking into account sex, age, comorbidities, tumor characteristics and hormonal levels.

To date, no data are available on the effects of long-term combined treatment with somatostatin analogues (SA) and pegvisomant (PEG) on cardiovascular complications in acromegaly. The current study aimed at investigating the effects of long-term SA + PEG on cardiac structure and performance. Thirty-six patients (14 M, 22 F, aged 52.3 ± 10.2 years) entered this study. Weight, BMI, systolic (SBP) and diastolic (DBP) blood pressure, IGF-I, fasting glucose (FG), fasting insulin (FI), HOMA-IR, HbA1c, and lipids were evaluated at baseline (T0), after long-term (median 36 months) SA (T1), after 12 (T12) and 60 (T60) months of SA + PEG, and at last follow-up (LFU, median 78 months). At each time point, all patients underwent echocardiography. At T1, induced a slight but not significant decrease in IGF-I (p = 0.077), whereas FI (p = 0.004), HOMA-IR (p = 0.013), ejection fraction (EF, p = 0.013), early (E) to late (A) ventricular filling velocities (E/A, p = 0.001), and isovolumetric relaxation time (IVRT, p = 0.000) significantly improved. At T12, IGF-I (p = 0.000) significantly reduced compared to T0, and FI (p = 0.001), HOMA-IR (p = 0.000), LVMI (p = 0.000), and E/A (p = 0.006) further improved compared to T1. At T60, FI (p = 0.027), HOMA-IR (p = 0.049), and E/A (p = 0.005) significantly improved as compared to T1. At LFU IGF-I normalized in 83.3 %, FI (p = 0.000), HOMA-IR (p = 0.000), LVMi (p = 0.000), and E/A (p = 0.005) further improved as compared to T1. PEG dose significantly correlated with LVMi at T12 (r = 0.575, p = 0.000) and T60 (r = 0.403, p = 0.037). Long-term PEG addition to SA improves cardiac structure and performance, particularly diastolic dysfunction, in acromegalic patients resistant to SA.

Background: Somatostatin analogues therapy is an important part of the acromegalic patients’ treatment. Aim: Assessment of treatment efficiency for patients with acromegaly using different doses of somatostatin analogues. Materials and methods: The data of 128 acromegaly patients registered in Moscow Region were analyzed, 79 (61.7%) of them were treated with somatostatin analogues. The treatment was started with a dose of 20 mg. If the target levels of growth hormone (GH) and type 1 insulin-like growth factor (IGF-1) were not achieved within 6-12 months, the dose was increased to 30 mg, and then to 40 mg. If GH and IGF-1 levels fell under the target values, the dose was decreased to 10 mg. The rate of achievement of optimal GH and IGF-1 levels was analyzed depending on the somatostatin analogue doses used. Results: The percentage of the acromegalic patients who were under the first and the second lines of drug therapy, was almost similar: 55.7 and 44.3%, respectively. Sandostatin LAR in dose of 10 mg was given to 4 (5.1%) of 79 patients, 20 mg – to 33 (41.8%), 30 mg – to 11 (13.9%), and 40 mg – to 31 (39.2%) patients. The target levels of GH and IGF-1 were achieved in 57.6, 54.5, and 32.2% of patients, who received preparation in doses 20, 30, and 40 mg, respectively. Achievement of, at least, one planned criterium (GH or IGF-1) was additionally noted in 10 of 33 (30.3%), 4 of 11 (36.2%), and 9 of 31 (29%) patients within these study groups. The rate of side effects didn’t increase with the raising of оctreotide dose. Conclusion: Application of long-acting release octreotide (Sandostatin-LAR) in doses of 30 and 40 mg is safe and allows to increase percentage of acromegalic patients who achieve a biochemical control over acromegaly.

Purpose To characterise efficacy and safety of (177)Lu-DOTATOC as agent for peptide receptor radiotherapy (PRRT) of advanced neuroendocrine tumours (NET). Patients and methods Fifty-six subjects with metastasized and progressive NET (50% gastroenteral, 26.8% pancreatic, 23.2% other primary sites) treated consecutively with (177)Lu-DOTATOC were analysed retrospectively. Subjects were administered (177)Lu-DOTATOC (mean 2.1 cycles; range 1-4) as 7.0GBq (median) doses at three-monthly intervals. Efficacy was analysed using CT and/or MRI according to RECIST 1.1 criteria and results were stratified for the number of administered cycles and the primary tumour origin. Results In the total NET population (A), median progression-free (PFS) and overall survival (OS) were 17.4 and 34.2 months, respectively, assessed in a follow-up time (mean ± SD) of 16.1 ± 12.4 months. In patients receiving more than one cycle, mean follow-up time was 22.4 ± 11.0 months for all NETs (B) and PFS was 32.0 months for all NETs (B), 34.5 months for GEP-NET (C), and 11.9 months for other NETs (D). Objective response rates (Complete/Partial Responses) were 33.9%, 40.6%, 54.2%, and 0% for A, B, C, and D groups, respectively, while disease control rates in the same were 66.1%, 93.8%, 100%, and 75%. Complete responses (16.1%, 18.8% and 25.0% for groups A, B and C) were high, 78% of which were maintained throughout the follow up. There were no serious adverse events. One case of self-limiting grade 3 myelotoxicity was reported. Although 20% of patients had mild renal insufficiency at baseline, there was no evidence of exacerbated or de novo renal toxicity after treatment. Conclusion (177)Lu-DOTATOC is a novel agent for PRRT with major potential to induce objective tumour responses and sustained disease control in progressive neuroendocrine tumours, even when administered in moderate activities. The observed safety profile suggests a particularly favourable therapeutic index, including in patients with impaired bone marrow or renal function, which reflects a uniquely low uptake of (177)Lu-DOTATOC by normal organs.

Peritoneal mucinous carcinomatosis is an aggressive subtype of pseudomyxoma peritonei, which often leads to inoperable bowel obstruction and, ultimately, death. Due to the poor prognosis, treatment is often symptomatic and aimed at alleviating the symptoms - pain, nausea, and vomiting - associated with gastrointestinal obstruction. Due to their antisecretory activity, somatostatin analogues are commonly prescribed in such cases. In the case presented here, a patient diagnosed with disseminated peritoneal mucinous carcinomatosis of appendiceal origin responded well to symptomatic treatment with lanreotide Autogel® at a dose of 120 mg/28 days. More importantly, radiological evidence of a reduction in peritoneal ascites, indicative of antiproliferative activity, was observed. These findings are important, particularly given the negative impact of this disease on both quality of life and survival. This case adds to the growing body of evidence supporting the antiproliferative and antisecretory activity of lanreotide Autogel.

Thyrotropin (TSH)-secreting pituitary adenomas (TSH-oma) are rare and account for about 0.5-3% of all pituitary adenomas. Patients with TSH-oma present themselves mostly with central hyperthyroidism expressing increased circulating levels of TSH, free T4 and T3.1 TSH-omas are usually benign tumours and express somatostatin receptors subtypes 2 and 5. This article is protected by copyright. All rights reserved.

608 Background: Somatostatin analogue (SSA) use is indicated in acromegaly and neuroendocrine tumours for symptomatic relief and tumour control. Two long-acting SSAs (lanreotide and octreotide) are currently available, but comparative real-world data on their use are limited. This study evaluated SSA use and costs in Canada. Methods: Claims data from the IQVIA Private Drug Plan (PDP), Ontario Drug Benefit (ODB) program and Régie de l’assurance-maladie du Québec (RAMQ) were compiled. Injection burden, rescue medication use and costs were compared (using unpaired t-test or Wilcoxon test) over a 12-month period from first SSA prescription. Patients (pts) were eligible if the first prescription was dispensed Sept. 2015–Jun. 2018. Results: 908 pts were included: lanreotide 120 mg, N=375; octreotide long-acting release (LAR) 30 mg, N=533. Lanreotide treatment was associated with a lower weighted average injection burden for 12 months when compared to octreotide (12.54 vs 13.44 injections/pt, respectively; p

Prospective randomized investigation of the efficiency of somatostatin analogues and glucocorticoids in pancreatic fistula prevention after pancreatoduodenectomy by using.In period from December 2018 till March 2020 78 patients underwent pancreatoduodenectomy for pancreatobilliary tumors in department of abdominal surgery of National Medical Research Center of Surgery named after A.V. Vishnevsky. Intraoperative frozen section investigation of pancreatic functioning acinar structures (FAS) was held for all patients. 38 patients had more than 40% of FAC and were related with high risk of pancreatic fistula (PF), while 40 patients with less than 40% FAC were included in low risk of PF group. In both groups patients were randomized to main and control subgroups. In main subgroup of high risk group patients combination of somatostatin analogues and glucocorticoids was used, while in control subgroup patients received only somatostatin analogue. In low risk of PF group patients of main subgroup preventively got somatostatin analogue, while control group patients had no specific prophylaxis of PF. To assess the effect of drug prophylaxis on the development of pancreatic fistula we used logistic regression models with the inclusion of the drug use factor as an independent variable.25 patients were included in main subgroup of high risk group. Clinically relevant pancreatic fistula (CRPF) developed in 14 (56%) cases. From 13 patients of control subgroup CRPF developed in 5 (38%) cases. In main subgroup of low risk group 18 patients were included and 3 (16%) of them had CRPF. In control subgroup were 22 patients and there were no cases of CRPF.In our series combination of somatostatin analogue and glucocorticoid didn't show efficiency in prevention of CRPF in high risk patients, although difference between subgroups wasn't statistically significant (Проспективное рандомизированное изучение эффективности профилактики послеоперационного свища (ПС) после панкреатодуоденальной резекции (ПДР) за счет применения аналогов соматостатина и глюкокортикоидов.В отделении абдоминальной хирургии НМИЦ хирургии им. А.В. Вишневского с декабря 2018 г. по март 2020 г. было выполнено 78 ПДР по поводу опухолей билиопанкреатодуоденальной области. Интраоперационно определялось количество функционирующих ацинарных структур (ФАС) в срезе поджелудочной железы (ПЖ). Более 40% ФАС выявлено у 38 больных, которые были отнесены к группе высокого риска развития ПС. Менее 40% ФАС обнаружено у 40 больных, которые составили группу низкого риска. Пациенты группы высокого риска были разделены путем рандомизации на основную и контрольную подгруппы. В основной подгруппе в качестве профилактики ПС использовали гидрокортизон и синтетические аналоги соматостатина. В контрольной подгруппе пациенты получали только синтетические аналоги соматостатина. В группе низкого риска возникновения ПС пациенты также были разделены путем рандомизации на основную подгруппу и контрольную. В основной подгруппе пациенты получали синтетические аналоги соматостатина. В контрольной подгруппе специфическая медикаментозная профилактика ПС не проводилась. Для оценки влияния медикаментозной профилактики на развитие ПС использовались логистические регрессионные модели с включением фактора применения препарата в качестве независимой переменной.В группе пациентов высокого риска ПС в основную подгруппу вошли 25 пациентов, клинически значимый ПС возник в 14 (56%) случаях, в контрольной подгруппе были 13 больных, из них клинически значимый ПС отмечен у 5 (38%). В группе пациентов с низким риском ПС в основную подгруппу были включены 18 больных; клинически значимый ПС возник у 3 (16%), в контрольную подгруппу вошли 22 пациента, у которых клинически значимого ПС зафиксировано не было.Комбинация глюкокордикоидов и аналогов соматостатина при высоком риске возникновения ПС после ПДР не снижает частоту развития ПС, лучшие результаты были достигнуты при изолированном применении аналогов соматостатина. У больных с низким риском возникновения ПС аналоги соматостатина не привели к сокращению количества ПС.

Lanreotide autogel is a synthetic somatostatin analogue which has been FDA and EMA approved for unresectable, well to moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumor. Its action is mediated by its affinity to somatostatin receptors, especially sst2 and sst5 receptors. Its longer half-life offers the convenience of 4-week dosing over the need for frequent injections of short-acting somatostatin analogues. Areas covered: Lanreotide ATG offers progression-free survival benefit in locally advanced or metastatic neuroendocrine tumor (NET) compared to placebo, reflecting a strong antiproliferative signal. As lanreotide is commonly used for management of NET, it is imperative to recognize and appropriately manage any drug-related toxicities. In this review, we will provide an overview of the toxicity with lanreotide and its management. Expert opinion: Lanreotide is highly effective in managing carcinoid symptoms and has a robust anti-tumor effect in NET. Overall, it is well tolerated with low rates of treatment discontinuation due to toxicity. It's toxicity profile is mostly predictable, and patients should be informed of the transient nature of some of the upfront toxicities.

Background/Aims: Congenital hyperinsulinism (CHI) is a rare disease characterized by recurrent severe hypoglycemia. In the diffuse form of CHI, pharmacotherapy is the preferred choice of treatment. Long-acting somatostatin analogues have been used in children as off-label medication. However, the efficacy, outcomes, and adverse effect profiles of long-acting somatostatin analogues have not been described in multicentered studies. The aim of this retrospective study is to summarize the experience with long-acting somatostatin analogues in a large group of children with CHI. Methods: Data were obtained retrospectively from 27 patients with CHI who received long-acting somatostatin analogues in 6 different centers in Europe. These included information on glycemic stability, auxology, and adverse effect profile in clinical follow-up assessments. Results: Blood glucose control improved in most patients (89%). No life-threatening side effects occurred. Thirteen patients (48%) experienced side effects; in 3 patients (11%), the side effects were the main reason for discontinuation of the treatment. The most frequent side effect was elevated liver enzymes (n = 10, 37%). Conclusion: Long-acting somatostatin analogues are effective in glycemic control of patients with CHI. However, in 37% of all patients increased liver enzymes were observed. It is important to monitor liver function in all patients receiving long-acting somatostatin analogue therapy.

Purpose: Analyze the role of somatostatin analogues (SSAs) in the treatment of sporadic and MEN1-related gastrinomas, trying to define whether recent trials have changed the landscape of gastrinoma therapy. Methods: We evaluate the rationale of SSA use in the treatment of gastrinomas, summarize the current literature concerning the effect of SSAs on the control of Zollinger-Ellison syndrome (ZES) and gastrinomas tumor progression and discuss their role in the most recent guidelines. Results: The medical treatment of gastrinoma and related ZES is aimed at controlling acid hypersecretion and tumor progression, in inoperable patients. The use of proton pump inhibitors (PPIs) to control the syndrome is a cornerstone in the ZES therapy. SSAs are not usually indicated for antisecretory purpose, because PPIs are considered the treatment of choice, due to their long lasting high efficacy and oral availability. The antiproliferative effect of SSAs has been established by two placebo-controlled trials that have clearly demonstrated a significant increase in progression free survival in patients affected by non-functioning well-differentiated advanced neuroendocrine tumors (NETs). The recent ENETS guidelines recommend the use of SSAs in advanced well differentiated NETs as antiproliferative agents. Conclusions: The high sstr-expression in gastrinomas make them highly responsive to SSAs and support the use of such drugs to counteract the tumour growth in patients not amenable to surgical cure. Unfortunately, limited data, mainly case reports or small series, support the use of SSAs in advanced gastrinomas, therefore, it is difficult to quantify their ability to control tumour growth and disease progression.

PurposeIn the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m2) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.MethodsAssessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan.FindingsIn 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss ≥3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.ImplicationsUp to 32.5% of patients treated with telotristat ethyl experienced significant, dose-dependent weight gain, associated with reduced diarrhea severity and improved biochemical and metabolic parameters. Improved nutritional status could be an additional aspect of telotristat ethyl efficacy among patients with functioning metastatic neuroendocrine tumors.